iCell® Neurons Enable Alzheimer’s Disease Modeling

Research demonstrate potential use of iCell® Neurons in high throughput screening at GlaxoSmithKline.

Cellular Dynamics International (CDI) has announced the publication of research demonstrating the use of human iPSC-derived iCell® Neurons to model Alzheimer’s disease (AD) and how they may be used in high throughput drug screening.

This research was performed by the lab of Zhong Zhong, Ph.D., head of discovery in the regenerative medicine group within GlaxoSmithKline (GSK), and recently published online in Stem Cell Research (DOI 10.1016/j.scr.2012.11.005).

The GSK researchers used CDI’s commercially available iCell Neurons, comprised of human neurons with characteristic forebrain markers, to model neuronal loss in human AD brains by exposing them to β-amyloid 1-42 (Aβ1-42), a peptide known to be associated with AD.

Aβ1-42 builds up in the brains of those susceptible to the disease and acts as a plaque that causes progressive memory loss and cognitive decline.

Because iCell Neurons meet tight quality standards and are available commercially in large quantities, the researchers used this AD cellular model to screen hundreds of compounds and ultimately identified several small molecules that inhibited the Aβ1-42 toxicity.

This is the first known use of human iPSCs to model Alzheimer’s disease through Aβ1-42 toxicity in a drug screen and demonstrates the value of commercial-scale quantities of human iPSC-derived cells for use in disease modeling, drug discovery, and target validation.

“Prior to iCell Neurons, the research models available to study AD included mice, human postmortem tissues, and immortalized neuronal cell lines. These models all have severe physiologic and genetic limitations,” said Emile Nuwaysir, chief operating officer of CDI and co-author on the paper.

Nuwaysir continued, “To make rapid progress in AD research, it is critical to have a cellular model that accurately recapitulates normal and disease pathology. We were excited to work with a team as talented as Dr. Zhong’s to perform this study, which demonstrated that when you have a physiologically relevant and reproducible system like iCell Neurons as the basis for your screening platform, you can make rapid and dramatic discoveries.”

Robert Palay, chief executive officer of CDI, added, “CDI’s iCell Neurons exhibit true functional human biology. This study demonstrated the potential of high throughput screening on iCell Neurons in identifying novel therapeutic compounds. The work contained in this paper is just another example confirming that CDI’s ability to supply our customers with fully functional, standardized human cells enables pharmaceutical scientists to quickly discover new drug candidates, particularly for challenging pathologies such as neurodegenerative diseases.”

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